The Lateral Habenula Circuitry: Reward Processing and Cognitive Control

Abstract

There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown. To begin to address this unresolved question, we present here emerging cross-species perspectives with a goal to provide a more refined understanding of the role of the LHb circuits in reward and cognition. We begin by highlighting recent findings from rodent experiments using optogenetics, electrophysiology, molecular, pharmacology, and tracing techniques that reveal diverse neural phenotypes in the LHb circuits that may underlie previously undescribed behavioral functions. We then discuss results from electrophysiological studies in macaques that suggest that the LHb cooperates with the anterior cingulate cortex to monitor action outcomes and signal behavioral adjustment. Finally, we provide an integrated summary of cross-species findings and discuss how further research on the connectivity, neural signaling, and physiology of the LHb circuits can deepen our understanding of the role of the LHb in normal and maladaptive behaviors associated with mental illnesses and drug abuse.

Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder

“…Given renewed interest in the reproducibility of psychological and, in particular, neuroimaging results [67-69], replication of these task-based outcomes within a larger sample than that from the original report [45] and across multiple scanning sessions is noteworthy. In addition, our results extend the body of extant literature on human habenula function [34,55,56,70] by providing further evidence for the region's role in reward processing. Specifically, we explored the interrelation of brain activity between pairs of task-related regions (i.e., correlations between feedback-related activity from the habenula, insula, ACC, and striatum).…”

“…We observed that as the responsivity of the habenula increased to negative feedback across participants, the insula's and ACC's responsivity to negative feedback also increased, while conversely, the ventral striatum's responsivity to positive feedback decreased. These exploratory correlational outcomes are generally consistent with the habenula's role in negative outcome processing [45,55], within a larger negative outcome processing neurocircuitry [54,70], and in inhibiting activity of DAergic neurons which project to the ventral striatum [46,58].…”

Lateral Preoptic Control of the Lateral Habenula through Convergent Glutamate and GABA Transmission

“…The LHb has been proposed to play a role in the integration of information about behavioral outcomes, bodily states, and environmental stimuli, and in the evaluation of this information in order to guide motivated behavior (Baker et al, 2016; Kawai et al, 2015; Matsumoto and Hikosaka, 2007; Stopper and Floresco, 2014). In addition, several studies have now demonstrated that changes in the balance of glutamatergic and GABAergic integration by the LHb are associated with mental disorders (Maroteaux and Mameli, 2012; Meye et al, 2016; Shabel et al, 2014).…”

Control of behavioral flexibility by the lateral habenula

“…This tonic task related activity may relate to velocity correlated activity observed in the LHb during task performance (Sharp et al 2006; Baker et al 2015), a possibility that should be explored as a mechanism for tracking ongoing behavior and relating it to outcomes. Others have reviewed in detail connections of the LHb with the primate dopamine reward prediction error signals first described by Schultz (1998) (Proulx et al 2014; Baker et al 2016a). The role of the LHb in contributing to reward prediction error signals in dopamine neurons is likely a contributor to its role in behavioral flexibility tasks.…”